Lu Chun-Lei, Xu Jian, Yao Hao-Jie, Luo Kun-Lun, Li Jie-Ming, Wu Tao, Wu Guo-Zhong
Department of Gastrointestinal Surgery, No. 101 Hospital of PLA, No. 101, Xingyuan Bei Road, Wuxi, Jiangsu, 214044, China.
Tumour Biol. 2016 Jan;37(1):1319-25. doi: 10.1007/s13277-015-3873-5. Epub 2015 Aug 21.
The adhesion mediated drug resistance in cancer cells resulted from adhesion of the extracellular matrix is a major cause for multidrug resistance (MDR) and leads chemotherapeutic failure for colon cancer. In this study, we explored the role of 67-kDa laminin receptor (67LR) in chemotherapeutic drug resistance in colon cancer cells. SiRNA-mediated knockdown of 67LR decreased the cell adhesion when laminins were applied. Moreover, 67LR knockdown increased the expression of pro-apoptotic gene Bax but inhibited the expression of anti-apoptotic gene Bcl-2. Enhanced apoptosis was observed in 67LR siRNA-transfected SW480 cell when the cell was treated with doxorubicin for apoptosis induction. Furthermore, MTT assay revealed that the IC50 of chemotherapeutic toward SW480 cell adhesion to laminins was reduced after 67LR knockdown, indicating there was a significant increase of drug sensitivity in SW480 cell. In conclusion, our study demonstrated that 67LR plays a considerable role in the development of colon cancer MDR.
癌细胞中由细胞外基质黏附介导的耐药性是多药耐药(MDR)的主要原因,导致结肠癌化疗失败。在本研究中,我们探讨了67 kDa层粘连蛋白受体(67LR)在结肠癌细胞化疗耐药中的作用。当应用层粘连蛋白时,siRNA介导的67LR敲低降低了细胞黏附。此外,67LR敲低增加了促凋亡基因Bax的表达,但抑制了抗凋亡基因Bcl-2的表达。在用阿霉素诱导凋亡处理时,在转染了67LR siRNA的SW480细胞中观察到凋亡增强。此外,MTT分析显示,67LR敲低后,化疗药物对SW480细胞与层粘连蛋白黏附的IC50降低,表明SW480细胞的药物敏感性显著增加。总之,我们的研究表明67LR在结肠癌MDR的发生中起重要作用。